The specific objectives of this project are: (a) to synthesize congeners of synthetic compounds with confirmed activity; (b) to design and synthesize prodrugs and other compounds that possess elements of both congener and prodrugs; (c) to synthesize compounds related to products of natural origin and other related heterocycles. There are several compounds in the NCI files, where progress is hampered by sub-DN2 level activity, poor solubility and/or stability. In an attempt to overcome these problems, and, in addition, make possible the flow of new compounds specifically designed to mitigate these difficulties, we propose to continue this project. The objectives are to design and synthesize (1) congeners of lead compounds to enhance the activity or broaden the antitumor spectrum; (2) prodrugs that are chemically altered transport forms of compounds to modify both biological and pharmaceutical properties, such as (a) improved bio-availability by increasing aqueous solubility; (b) increased compound stability; and (3) compounds related to products of natural origin. These modifications may include partial structures, analogs and novel heterocycles.